Análise estatística de agregados celulares na formação de redes vasculares

Abstract

In this work we present an experimental study of vasculogenesis in chicken embryos from a physics point of view. We use statistical physics and the network science to characterize the self-organization of cell clusters forming a single vascular network. The vascular network formation was observed by means bright-field microscopy during 15 hours of embryonic development. We quantity the self-organization of endothelial cell clusters forming a single vascular network in control embryos and in embryos treated with bevacizumab (Avastin), an antibody that inhibits the signalization of the vascular endothelial growth factor, VEGF. In this work our aim is twofold: first we propose to study vasculogenesis on control embryos, it means without VEGF restriction, in order to characterize the vascular network formation and discuss physical principles that may be driven the collective behavior in the system. Second, we characterize the vascular network formation applying a drug that binds to VEGF decreasing the free VEGF in extracellular matrix. In order to get quantitative parameters from the original images sequence we developed a methodology to extract binary patterns, network topologies and the adjacency matrices. This methodology allows us to make an accurate characterization of the endothelial cell clusters forming a single vascular network in control embryos and in Avastin-treated embryos. This characterization accounts for statistical parameters such as vessels density, cord length, number of cell clusters, fractal dimension and the largest cluster density. Also we characterized the system by means of the usual network metrics suchas: the degree distribution, average clustering coeficient, average short path length, and assortativity among others. From these studies we were able to monitor the growth of the largest connected cluster in the system and provide quantitative evidences of the disruptive effects that Avastin has on the tree structure of vascular networks.